The objective of this project is to investigate extracellular matrix-cell interactions employing an experimental system of matrix-induced endochondral bone differentiation. This experimental model further affords a method to undertake systematic studies on the biochemistry and physiology of endochondral bone formation. Subjects currently under investigation are: (1) the local mitogenic effects of collagenous bone matrix; (2) changes in proline-synthetic and degradative enzymes during matrix-induced cartilage and bone development; (3) immunofluorescent localization of type IV collagen and laminin during endochondral bone differentiation and regulation by pituitary growth hormone; (4) influence of magnesium depletion on endochondral bone formation; (5 influence of experimental diabetes and insulin on cartilage and bone differentiation; and (6) role of collagen-crosslinking in mineralization of bone.